Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types

Rhesus cytomegalovirus infection of rhesus macaques has emerged as a model for human cytomegalovirus pathogenesis. The UL128-UL131 locus of the human virus is a primary determinant for viral entry into epithelial cells, an important cell type during cytomegalovirus infection. Rhesus cytomegalovirus strain 68-1 spreads slowly when grown in cultured rhesus epithelial cells, and it does not code for ORFs corresponding to UL128 and the second exon of UL130. We repaired the UL128-UL131 locus of strain 68-1, using rhesus cytomegalovirus strain 180.92 as template, to generate BRh68-1.1. We also repaired a mutation in the UL36 ORF in BRh68-1.1 to make BRh68-1.2. Both repaired derivatives replicate much more efficiently than parental 68-1 virus in rhesus epithelial cells, suggesting that strain 68-1 may be attenuated. Intriguingly, BRh68-1.1 and BRh68-1.2 replicate efficiently in cultured human epithelial cells and endothelial cells. The extended human cell host range of the repaired viruses raises the possibility that rhesus cytomegalovirus-like viruses will be found in humans.